Amyloid neuropathology in the single Arctic APP transgenic model affects interconnected brain regions
| Autor: | Jan Näslund, Karin Dillner Bergstedt, Caroline Graff, Annica Rönnbäck, Hanna Sagelius, Bengt Winblad, Gunilla T. Westermark |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Aging Amyloid Amyloid beta BACE1-AS Enzyme-Linked Immunosorbent Assay Mice Transgenic Neuropathology Hippocampus Amyloid beta-Protein Precursor Mice Alzheimer Disease mental disorders Amyloid precursor protein Animals Humans Senile plaques Microscopy Immunoelectron Analysis of Variance Amyloid beta-Peptides biology General Neuroscience P3 peptide Age Factors Peptide Fragments Biochemistry of Alzheimer's disease Disease Models Animal Mutation biology.protein Female Neurology (clinical) Geriatrics and Gerontology Neuroscience Developmental Biology |
| Zdroj: | Neurobiology of aging. 33(4) |
| ISSN: | 1558-1497 |
| Popis: | The Arctic APP mutation (E693G) within the amyloid β (Aβ) domain of amyloid precursor protein (APP) leads to dementia with clinical features similar to Alzheimer's disease (AD), which is believed to be mediated via increased formation of protofibrils. We have generated a transgenic mouse model, TgAPParc, with neuron-specific expression of human amyloid precursor protein with the Arctic mutation (hAPParc), showing mild amyloid pathology with a relatively late onset. Here we performed a detailed analysis of the spatiotemporal progression of neuropathology in homozygous TgAPParc, focusing on intracellular Aβ and diffuse Aβ aggregates rather than amyloid plaques. We show that the neuropathology in homozygous TgAPParc mice starts with intracellular Aβ aggregates, which is followed by diffuse extracellular Aβ deposits in subiculum that later expands to brain regions receiving neuronal projections from regions already affected. Together this suggests that the pathology in TgAPParc mice affects interconnected brain regions and may represent a valuable tool to study the spread and progression of neuropathology in Alzheimer's disease. |
| Databáze: | OpenAIRE |
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